Valine, leucine, and isoleucine are essential branched chain amino acids (BCAAs). When BCAA metabolism is genetically impaired in human, serum levels of BCAA and/or their metabolites rise considerably, causing severe neurological dysfunction. The first step in BCAA catabolism is catalyzed by branched chain aminotransferase (BCAT). Hypervalinemia and hyperleucine-isoleucinemia caused by BCAT gene mutation in human have not been reported previously. A 25-year-old man presented with headache complaints and mild memory impairment for about six years. Brain MRI showed symmetric white matter abnormal signals. Metabolic studies revealed remarkably elevated plasma valine and leucine concentrations. Maple syrup urine disease (MSUD) diagnosis was not supported since all genes for the branched-chain alpha-keto acid dehydrogenase complex (BCKD) gene were normal. Interestingly, two heterogeneous BCAT2 gene mutations were found in the patient, including c.509G > A (p.Arg170Gln) and c.790G > A (p.Glu264Lys). In addition, c.509G > A (p.Arg170Gln) and c.790G > A (p.Glu264Lys) were found in his father and mother, respectively, suggesting an autosomal recessive disorder. BCAT2 functional studies demonstrated that the two BCAT2 gene mutations resulted in decreased BCAT2 enzyme activity. After treatment with vitamin B6, the levels of BCAA, especially valine were remarkably decreased and brain MRI lesions were improved. These findings suggest a new type of branched chain amino acid metabolism disorder. This rare case provides great insight into the further understanding of BCAA metabolism and its defect in human. BCAT2 gene mutations can cause hypervalinemia and hyperleucine-isoleucinemia, which are associated with brain white matter lesions.